scholarly journals HCV Pit Stop at the Lipid Droplet: Refuel Lipids and Put on a Lipoprotein Coat before Exit

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 233 ◽  
Author(s):  
Gabrielle Vieyres ◽  
Thomas Pietschmann
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplet ◽  
Cell Biology ◽  
Lipid Droplets ◽  
Protein Translocation ◽  
Droplet Surface ◽  
Replication Cycle ◽  
Virion Assembly ◽  
Host Interactions ◽  
Virus Replication Cycle

The replication cycle of the liver-tropic hepatitis C virus (HCV) is tightly connected to the host lipid metabolism, during the virus entry, replication, assembly and egress stages, but also while the virus circulates in the bloodstream. This interplay coins viral particle properties, governs viral cell tropism, and facilitates immune evasion. This review summarizes our knowledge of these interactions focusing on the late steps of the virus replication cycle. It builds on our understanding of the cell biology of lipid droplets and the biosynthesis of liver lipoproteins and attempts to explain how HCV hijacks these organelles and pathways to assemble its lipo-viro-particles. In particular, this review describes (i) the mechanisms of viral protein translocation to and from the lipid droplet surface and the orchestration of an interface between replication and assembly complexes, (ii) the importance of the triglyceride mobilization from the lipid droplets for HCV assembly, (iii) the interplay between HCV and the lipoprotein synthesis pathway including the role played by apolipoproteins in virion assembly, and finally (iv) the consequences of these complex virus–host interactions on the virion composition and its biophysical properties. The wealth of data accumulated in the past years on the role of the lipid metabolism in HCV assembly and its imprint on the virion properties will guide vaccine design efforts and reinforce our understanding of the hepatic lipid metabolism in health and disease.

scholarly journals A conserved family of proteins facilitates nascent lipid droplet budding from the ER

2015 ◽  
Vol 211 (2) ◽  
pp. 261-271 ◽  
Author(s):  
Vineet Choudhary ◽  
Namrata Ojha ◽  
Andy Golden ◽  
William A. Prinz
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Caenorhabditis Elegans ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
De Novo ◽  
Fat Storage ◽  
Higher Eukaryotes ◽  
Er Membrane

Lipid droplets (LDs) are found in all cells and play critical roles in lipid metabolism. De novo LD biogenesis occurs in the endoplasmic reticulum (ER) but is not well understood. We imaged early stages of LD biogenesis using electron microscopy and found that nascent LDs form lens-like structures that are in the ER membrane, raising the question of how these nascent LDs bud from the ER as they grow. We found that a conserved family of proteins, fat storage-inducing transmembrane (FIT) proteins, is required for proper budding of LDs from the ER. Elimination or reduction of FIT proteins in yeast and higher eukaryotes causes LDs to remain in the ER membrane. Deletion of the single FIT protein in Caenorhabditis elegans is lethal, suggesting that LD budding is an essential process in this organism. Our findings indicated that FIT proteins are necessary to promote budding of nascent LDs from the ER.

scholarly journals Multifunctional pyrazoline based AIEgens: real-time tracking and specific protein “fishing” of lipid droplets

2019 ◽  
Vol 10 (39) ◽  
pp. 9009-9016 ◽  
Author(s):  
Na Zhao ◽  
Yan Li ◽  
Weiyao Yang ◽  
Jiabao Zhuang ◽  
Yue Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Real Time ◽  
Intracellular Ph ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Specific Protein ◽  
Related Protein ◽  
Dual Color ◽  
Real Time Tracking

A series of multifunctional pyrazoline based AIEgens were developed for real-time tracking of lipid metabolism, reversibly monitoring intracellular pH in dual-color mode and specific labeling of lipid droplet related protein.

scholarly journals Perilipin-related protein regulates lipid metabolism in C. elegans

2015 ◽  
Author(s):  
Ahmed A. Chughtai ◽  
Filip Kaššák ◽  
Markéta Kostrouchová ◽  
Jan Philipp Novotný ◽  
Michael W. Krause ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Fat Metabolism ◽  
Droplet Surface ◽  
Surface Proteins ◽  
Related Protein ◽  
Additional Mechanism ◽  
C Elegans ◽  
Functional Studies ◽  
Gene Inhibition

The perilipins are lipid droplet surface proteins that contribute to fat metabolism by controlling the access of lipids to lipolytic enzymes. Perilipins have been identified in organisms as diverse as metazoa, fungi, and amoebas but strikingly not in nematodes. Here we identify the protein encoded by the W01A8.1 gene in Caenorhabditis elegans as the closest homologue of metazoan perilipin. We demonstrate that nematode W01A8.1 is a cytoplasmic protein residing on lipid droplets. Human perilipins 1 and 2 localize in transgenic C. elegans on the same structures as proteins expressed from W01A8.1 gene. Inhibition and elimination of W01A8.1 affects the appearance of lipid droplets especially visible as the formation of large lipid droplets localized around the dividing nucleus during the early zygotic divisions. This phenomenon disappears in later stages of embryogenesis indicating the existence of an additional mechanism of lipid regulation in C. elegans. Our results demonstrate that perilipin-related regulation of fat metabolism is conserved in nematodes and provide new possibilities for functional studies of lipid metabolism.

scholarly journals Seipin-Mediated Contacts as Gatekeepers of Lipid Flux at the Endoplasmic Reticulum–Lipid Droplet Nexus 

Contact ◽  
2020 ◽  
Vol 3 ◽  
pp. 251525642094582
Author(s):  
Veijo T. Salo ◽  
Maarit Hölttä-Vuori ◽  
Elina Ikonen
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Recent Work ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Intimate Relationship

Lipid droplets (LDs) are dynamic cellular hubs of lipid metabolism. While LDs contact a plethora of organelles, they have the most intimate relationship with the endoplasmic reticulum (ER). Indeed, LDs are initially assembled at specialized ER subdomains, and recent work has unraveled an increasing array of proteins regulating ER-LD contacts. Among these, seipin, a highly conserved lipodystrophy protein critical for LD growth and adipogenesis, deserves special attention. Here, we review recent insights into the role of seipin in LD biogenesis and as a regulator of ER-LD contacts. These studies have also highlighted the evolving concept of ER and LDs as a functional continuum for lipid partitioning and pinpointed a role for seipin at the ER-LD nexus in controlling lipid flux between these compartments.

In-depth characterization of the chikungunya virus replication cycle

2021 ◽  
Author(s):  
Erik V. S. Reis ◽  
Beatriz M. Damas ◽  
Diogo C. Mendonça ◽  
Jônatas S. Abrahão ◽  
Cláudio A. Bonjardim
Keyword(s):  
Virus Replication ◽  
Chikungunya Virus ◽  
Replication Cycle ◽  
New Drugs ◽  
Biological Assays ◽  
Host Interactions ◽  
Virion Release ◽  
Long Time ◽  
Membrane Protrusions ◽  
Virus Replication Cycle

The chikungunya virus has spread globally with a remarkably high attack rate. Infection causes arthralgic sequelae that can last for years. Nevertheless, there are no specific drugs or vaccines to contain the virus. Understanding the biology of the virus, such as its replication cycle, is a powerful tool to identify new drugs and comprehend virus-host interactions. Even though the chikungunya virus has been known for a long time (first described in 1952), many aspects of the replication cycle remain unclear. Furthermore, part of the cycle is based on observations of other alphaviruses. In this study, we used electron and scanning microscopy, as well as biological assays, to analyze and investigate the stages of the chikungunya virus replication cycle. Based on our data, we found other infection cellular activities than those usually described for the chikungunya virus replication cycle, i.e. we show particles enveloping intracellularly without budding in a membrane-delimited morphogenesis area; and we also observed virion release by membrane protrusions. Our work provides novel details regarding the biology of chikungunya virus and fills gaps in our knowledge of its replication cycle. These findings may contribute to a better understanding of virus-host interactions and support the development of antivirals. IMPORTANCE The understanding of virus biology is essential to containing virus dissemination, and exploring the virus replication cycle is a powerful tool to do this. There are many points in the biology of the chikungunya virus that need to be clarified, especially regarding its replication cycle. Our incomplete understanding of chikungunya virus infection stages is based on studies with other alphaviruses. We systematized the chikungunya virus replication cycle using microscopic imaging in the order of infection stages: entry, replication, protein synthesis, assembly/morphogenesis, and release. The imaging evidence shows novel points in the replication cycle of enveloping without budding, as well as particle release by cell membrane protrusion.

scholarly journals Biogenesis of the multifunctional lipid droplet: Lipids, proteins, and sites

2014 ◽  
Vol 204 (5) ◽  
pp. 635-646 ◽  
Author(s):  
Albert Pol ◽  
Steven P. Gross ◽  
Robert G. Parton
Keyword(s):  
Energy Metabolism ◽  
Lipid Droplet ◽  
Cell Biology ◽  
Lipid Droplets ◽  
Recent Progress ◽  
Human Diseases ◽  
Membrane Synthesis ◽  
Specific Lipid

Lipid droplets (LDs) are ubiquitous dynamic organelles that store and supply lipids in all eukaryotic and some prokaryotic cells for energy metabolism, membrane synthesis, and production of essential lipid-derived molecules. Interest in the organelle’s cell biology has exponentially increased over the last decade due to the link between LDs and prevalent human diseases and the discovery of new and unexpected functions of LDs. As a result, there has been significant recent progress toward understanding where and how LDs are formed, and the specific lipid pathways that coordinate LD biogenesis.

Subcellular localization of skeletal muscle lipid droplets and PLIN family proteins OXPAT and ADRP at rest and following contraction in rat soleus muscle

2012 ◽  
Vol 302 (1) ◽  
pp. R29-R36 ◽  
Author(s):  
Rebecca E. K. MacPherson ◽  
Eric A. F. Herbst ◽  
Erica J. Reynolds ◽  
Rene Vandenboom ◽  
Brian D. Roy ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lipid Droplet ◽  
Protein Interactions ◽  
Lipid Droplets ◽  
Droplet Surface ◽  
Protein Protein Interactions ◽  
Muscle Lipid ◽  
Droplet Distribution ◽  
Associated Proteins ◽  
Skeletal Muscle Lipid

Skeletal muscle lipid droplet-associated proteins (PLINs) are thought to regulate lipolysis through protein-protein interactions on the lipid droplet surface. In adipocytes, PLIN2 [adipocyte differentiation-related protein (ADRP)] is found only on lipid droplets, while PLIN5 (OXPAT, expressed only in oxidative tissues) is found both on and off the lipid droplet and may be recruited to lipid droplet membranes when needed. Our purpose was to determine whether PLIN5 is recruited to lipid droplets with contraction and to investigate the myocellular location and colocalization of lipid droplets, PLIN2, and PLIN5. Rat solei were isolated, and following a 30-min equilibration period, they were assigned to one of two groups: 1) 30 min of resting incubation and 2) 30 min of stimulation ( n = 10 each). Immunofluorescence microscopy was used to determine subcellular content, distribution, and colocalization of lipid droplets, PLIN2, and PLIN5. There was a main effect for lower lipid and PLIN2 content in stimulated compared with rested muscles ( P < 0.05). Lipid droplet distribution declined exponentially from the sarcolemma to the fiber center in the rested muscles ( P = 0.001, r2= 0.99) and linearly in stimulated muscles (slope = −0.0023 ± 0.0006, P < 0.001, r2= 0.93). PLIN2 distribution declined exponentially from the sarcolemma to the fiber center in both rested and stimulated muscles ( P < 0.0001, r2= 0.99 rest; P = 0.0004, r2= 0.98 stimulated), while PLIN5 distribution declined linearly (slope = −0.0085 ± 0.0009, P < 0.0001, r2= 0.94 rest; slope=−0.0078 ± 0.0010, P = 0.0003, r2= 0.91 stimulated). PLIN5-lipid droplets colocalized at rest with no difference poststimulation ( P = 0.47; rest r2= 0.55 ± 0.02, stimulated r2= 0.58 ± 0.03). PLIN2-lipid droplets colocalized at rest with no difference poststimulation ( P = 0.48; rest r2= 0.66 ± 0.02, stimulated r2= 0.65 ± 0.02). Contrary to our hypothesis, these results show that PLIN5 is not recruited to lipid droplets with contraction in isolated skeletal muscle.

scholarly journals Perilipin-related protein regulates lipid metabolism in C. elegans

2015 ◽  
Author(s):  
Ahmed A. Chughtai ◽  
Filip Kaššák ◽  
Markéta Kostrouchová ◽  
Jan Philipp Novotný ◽  
Michael W. Krause ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Fat Metabolism ◽  
Droplet Surface ◽  
Surface Proteins ◽  
Related Protein ◽  
Additional Mechanism ◽  
C Elegans ◽  
Functional Studies ◽  
Gene Inhibition

The perilipins are lipid droplet surface proteins that contribute to fat metabolism by controlling the access of lipids to lipolytic enzymes. Perilipins have been identified in organisms as diverse as metazoa, fungi, and amoebas but strikingly not in nematodes. Here we identify the protein encoded by the W01A8.1 gene in Caenorhabditis elegans as the closest homologue of metazoan perilipin. We demonstrate that nematode W01A8.1 is a cytoplasmic protein residing on lipid droplets. Human perilipins 1 and 2 localize in transgenic C. elegans on the same structures as proteins expressed from W01A8.1 gene. Inhibition and elimination of W01A8.1 affects the appearance of lipid droplets especially visible as the formation of large lipid droplets localized around the dividing nucleus during the early zygotic divisions. This phenomenon disappears in later stages of embryogenesis indicating the existence of an additional mechanism of lipid regulation in C. elegans. Our results demonstrate that perilipin-related regulation of fat metabolism is conserved in nematodes and provide new possibilities for functional studies of lipid metabolism.

scholarly journals Getting a handle on lipid droplets: Insights into ER–lipid droplet tethering

2019 ◽  
Vol 218 (4) ◽  
pp. 1089-1091 ◽  
Author(s):  
Truc B. Nguyen ◽  
James A. Olzmann
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Human Cells ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Cell Biol ◽  
Membrane Contact

Lipid droplets (LDs) are hubs for lipid metabolism that form membrane contact sites with multiple organelles. In this issue, Hariri et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201808119) reveal the functions of Mdm1-mediated endoplasmic reticulum (ER)–LD tethering in yeast and Datta et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201808133) identify a role for the Mdm1 orthologue, Snx14, as an ER–LD tether that regulates lipid metabolism in human cells.

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